1,721,061 research outputs found
Natural compounds, antioxidant, and antiandrogens in the prevention of prostate cancer: in vivo evidences from murine models and human clinical studies.
No full textProstate cancer (PCa)is the most frequent malignant neoplasia in men. The number of cases has continuously increased over the past decades, partly due to the higher life expectancy.
Additional factors are the high caloric diet and lack of physical exercise, typically seen in the Western countries. Notably, up to 40% of cancer incidents are preventable by consuming a
healthy diet, regular physical activity, and maintenance of optimum body weight, and more than 20% by consuming vegetables and fruits. PCa represents an ideal candidate disease for chemoprevention. It is typically diagnosed in elderly men and even a modest delay in the neoplastic development could result in substantial reduction in the incidence of the clinically detectable disease.In this chapter we will review the history, the development, and the applications of some of the most common animal models of PCa,and we will discuss of the role of animal models in translational research
Neutrophils in anti-cancer immunological strategies: old players in new games
No full textThis review highlights the new "immunological identity" of neutrophils within the cytokine network and their role in biology of diseases, particularly in tumor biology. The latest preclinical evidence of their involvement in anti-cancer immunotherapeutic and prophylactic strategies will be discussed with particular reference to the real possibilities of transferring experimental results to a clinical setting
Reversal of P-glycoprotein-mediated multidrug resi stance in human sarcoma MES-SA/Dx-5 cells by nonsteroidal anti-inflammatory drugs
No full textMultidrug resistance (MDR) mediated by P-glycoprotein (P-gp) is one of the major reasons for the failure of cancer therapy. Several chemosensitizers are able to reverse in vitro MDR by inhibiting P-gp, although high toxicity limits their clinical application. In this study, we aimed to investigate the in vitro effectiveness of four common non-steroidal anti-inflammatory drugs (NSAIDs) such as Curcumin (Cur), Sulindac (Sul), Ibuprofen (Ibu) and NS-398 (NS) to inhibit P-gp activity at clinically achievable doses and to evaluate their potential use as sensitizers in anti-cancer chemotherapy. The human doxorubicin (doxo) resistant uterine sarcoma cells (MES-SA/Dx-5) expressing high levels of P-gp, were treated with different doxo concentrations in the presence or absence of NSAIDs. Cellular accumulation of doxo, cytotoxicity and apoptosis induction were measured in comparison with Verapamil, a specific P-gp inhibitor, used as a reference molecule. We found that Ibu, Cur and NS-398 enhanced significantly doxo retention, cytotoxicity and apoptosis on resistant MES-SA/Doxo-5 cells when compared with doxo alone. In contrast, no significant changes were found in resistant cells treated with Sul-doxo combinations. Our results demonstrate that Ibu, Cur and NS-398 below their therapeutic plasma concentrations were able to overcome P-gp-mediated MDR in MES-SA/Dx-5 cells. These findings provide the rationale for clinical studies of NSAIDs and/or derivatives as a new potential generation of chemosensitizers to improve effectiveness of the anti-cancer drugs in the treatment of human cancer
Biofilm formation by the emerging fungal pathogen Trichosporon asahii: development, architecture, and antifungal resistance.
No full textTrichosporon asahii is the most common cause of fatal disseminated trichosporonosis, frequently associated with indwelling medical devices. Despite the use of antifungal drugs to treat trichosporonosis, infection is often persistent and is associated with high mortality. This drove our interest in evaluating the capability of T. asahii to form a biofilm on biomaterial-representative polystyrene surfaces through the development and optimization of a reproducible T. asahii-associated biofilm model. Time course analyses of viable counts and a formazan salt reduction assay, as well as microscopy studies, revealed that biofilm formation by T. asahii occurred in an organized fashion through four distinct developmental phases: initial adherence of yeast cells (0 to 2 h), germination and microcolony formation (2 to 4 h), filamentation (4 to 6 h), and proliferation and maturation (24 to 72 h). Scanning electron microscopy and confocal scanning laser microscopy revealed that mature T. asahii biofilms (72-h) displayed a complex, heterogeneous three-dimensional structure, consisting of a dense network of metabolically active yeast cells and hyphal elements completely embedded within exopolymeric material. Antifungal susceptibility testing demonstrated a remarkable rise in the MICs of sessile T. asahii cells against clinically used amphotericin B, caspofungin, voriconazole, and fluconazole compared to their planktonic counterparts. In particular, T. asahii biofilms were up to 16,000 times more resistant to voriconazole, the most active agent against planktonic cells (MIC, 0.06 microg/ml). Our results suggest that the ability of T. asahii to form a biofilm may be a major factor in determining persistence of the infection in spite of in vitro susceptibility of clinical isolates
Effects of castration on the development of prostate adenocarcinoma from its precursor HGPIN and on the occurrence of androgen-independent poorly differentiated carcinoma in TRAMP mice.
No full textBALB-neuT Female Mice as a Dynamic Model of Mammary Cancer
No full textTumor-transplanted rodents are primarily adopted to study cancer
progression in vivo and the inhibitory potential of the immune system. Genetically engineered, cancer-prone mice, however, more closely mimic several features of human cancer. Inbred BALB/c female mice transgenic for the rat neu (Her-2/neu, ErbB-2) oncogene (BALB-neuT mice) constitute an intensively studied mammary cancer model.
Key features of this model include that (1) each of their ten mammary glands develops an independent carcinoma that slowly progresses from microscopic lesions to invasive tumors; (2) multiple in situ carcinomas are accompanied by greater dissemination of neoplastic cells into the bone marrow; (3) lung metastases are evident in the later stages; (4) over-expression of the protein product of the transgenic neu oncogene in the
newborn thymus induces the deletion of T cell clones reacting with high-affinity against it, while the step-wise progression of mammary lesions triggers negative regulation mechanisms that suppress antibody- and perforin-mediated immune surveillance
mechanisms. Thus, boosts of innate immunity delay cancer progression and vaccines administered when only early microscopic lesions are present provide lifelong protection, whereas their efficacy tails off when they are administered to mice with more advanced lesions. Because this model mimics some of the most critical features of human disease, it has been successfully used to investigate a number of therapeutic
agents, including the role of adaptor proteins (P130 cap), signal transducers (STAT3), phosphoinositide 3-kinase (PI3K), and oncogenic stress sensing kinases (MKK7) in neu-driven carcinogenesis, and assessment of the efficacy of braki therapy in the control of mammary cancer
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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